Vaccine adjuvants – Size and charge for alum or liposomes
Adjuvants for vaccination – How size and zeta may be relevant
What is an adjuvant?
Adjuvants are substances which are added to medicines to trigger and enhance an immune response to an antigen. In the USA, the most commonly-used adjuvant is alum (or various forms of Al for example aluminium sulfate, Al₂(SO₄)₃ aluminium hydroxide, amophous etc. ) and many vaccines in use today contain some aluminum components to help the vaccine work better. While the exact mechanisms of how adjuvants work is unclear to some extent, a typical adjuvant component is much larger than the antigen or antibody itself, often around 100 nm in radius.
In a paper entitled “Relationship between the size of nanoparticles and their adjuvant activity: Data from a study with an improved experimental design“, the authors showed increased immune response to 200 nm diameter particles compared with 700 nm diameter particles (both conjugated with a model antigen).
Another adjuvant class is liposomes, which can act both as immunostimulators and as delivery vehicles. As well as size, charge has been found to be relevant, with positively-charged liposomes shown to induce significant antibody response [see review by Schmidt, ST; Foged, C; Korsholm, KS; Rades, T; Christensen, D “Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators“]
Cell debris from bacteria or inactivated viruses may also act as a ‘natural’ adjuvant, meaning that additional adjuvants are not required in all types of vaccine. In recent years, subvisible particulates in biopharmaceutical products have gained attention for their potential to provoke immune responses against injected drug products potentially leading to the formation of anti-drug antibodies (ADAs).
How to size adjuvants and find their charge
One of the techniques available to size adjuvants (as well as other nanoparticles) is Dynamic Light Scattering (DLS), which analyzes intensity fluctuations in a small amount of sample to obtain the diffusion coefficient and the size distribution of the sample. Charge information is typically assessed by measuring zeta potential using Electrophoretic Light Scattering (ELS), where the influence of an applied electric field adds an overall direction to the random Brownian movement. The charge or zeta potential of the particle is a system parameter used to study the particle surface, and depends strongly on the overall make up of the buffer ( ionic strength, ion type, pH, additives, etc.).
Both DLS and ELS may be measured with the Malvern Zetasizer Nano.
Previously
- Why are my particles too small?
- A quick primer on dynamic light scattering
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